Figure 4:

Diagrammatic representation of potential mechanisms by which astrocyte-derived EVs (ADEVs) contribute to neuroinflammation and neurotoxicity in stroke, Parkinson’s disease (PD), and Amyotrophic lateral sclerosis (ALS) (A). Toxic ADEVs reduce axonal growth and impair brain repair in stroke, likely contribute to the degeneration of dopaminergic neurons through miR-34a and induce motoneuron death through mutant superoxide dismutase 1 (SOD1), transactive response DNA binding protein (TDP-43) and fused in sarcoma (FUS). Figure B illustrates the involvement of ADEVs in propagating inflammation in other neuroinflammatory conditions. When challenged with pro-inflammatory cytokine IL-1β, astrocytes in the brain shed EVs carrying specific proteins and miRNAs, which migrate rapidly into the liver through circulation and cause acute cytokine response by downregulating PARPα and upregulating NF-κB. Such a response leads to the transmigration of peripheral leukocytes into the brain through the disrupted blood-brain barrier.